Figure 1.

Spatial and temporal heterogeneity in NENs. Neuroendocrine neoplasms generally express SSTR2 on the tumour surface, and are well-differentiated tumours in the majority of cases. However, spatial heterogeneity within the primary tumour may lead to the presence of areas with lower expression of SSTR2 and/or a different Ki-67 index. This heterogeneity is also frequent in metastatic sites and can differ significantly from the primary lesion. The mTOR pathway is also commonly involved in the onset of the disease and is particularly relevant in distant metastases, although over time alternative pathways may be involved in tumour survival. Moreover, temporal heterogeneity that can be linked to treatment selective pressure may lead to significant changes in tumour biology that affect prognosis and survival.